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Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The current research aimed to evaluate the impact of berberine hydrochloride on improving cognitive function and neuroprotective effects in rats addicted to MA.In this study, 27 male Wistar rats were randomly assigned to three groups, including control, MA addiction, and MA addiction with berberine hydrochloride (100 mg/kg/d) orally during the three weeks of withdrawal. Two groups received self-administered inhaled MA for two weeks (up to 10 mg/kg). Following the experimental procedures, a Morris water maze (MWM) and shuttle box were used to assess memory, and hippocampal sections from the animals were examined for caspase-3, Ki-67, and glial fibrillary acidic protein (GFAP) expression.The obtained results from the Morris water maze (MWM) showed that berberine hydrochloride decreases (P0.01) the distance moved and the time spent to reach the hidden platform in the four-day learning trails phase and significant differences were observed in the distance moved, spent time, and frequency of motion in target quadrant on probe test day between groups. Berberine hydrochloride also reduced the latency of animals entering the dark chamber in the treated group compared to the control group (P0.05). A significant decrease in activation of caspases-3, higher percentages of Ki-67 expression, and an increase in glial fibrillary acidic protein (GFAP) expression of cells was observed in the addicted group compared to the berberine-treated and control groups (P0.05).Administration of berberine hydrochloride for 3 weeks improves cognitive function in MA addiction and it has potential neuroprotective efficacy.Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system.The berberine hydrochloride effects on improving cognitive function and neuroprotective.No approved pharmacotherapy, as well as confirmed medication, is available to treat MA abuse.Methamphetamine (MA) is known as a strong addictive stimulant with high addiction and no approved pharmaco-therapy, as well as confirmed medication, is available to treat MA abuse. The study on the long-term effect of MA exposure on cognitive function during an object recognition memory test showed cognitive dysfunction after MA exposure. Berberine can reduce induced amnesia, which can be due to the increased peripheral and central cholinergic neuronal system functions, in addition, the most important mechanism in the protective effect of berberine against amnesia is the inhabitation of inflammation; however, the berberine impact on cells should be more investigated.

Chronic methamphetamine (METH) abuse is recognized as an important risk factor for cognitive impairment. A plant-based isoquinoline alkaloid, Berberine hydrochloride (BER), shows memory and cognition enhancement properties. Due to the aim of the present study which is to investigate the influence of BER administration on METH-induced cognitive deficits, we investigated neurotrophin signaling including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) as a possible mechanism by which BER exerts its cognitive improvement influences.In this experimental study, thirty-two male Wistar rats were randomly classified into four groups, including non-treated control, intubated control, METH-inhaled, and METH-inhaled + BER-intubated. Rats in the METH-inhaled group underwent METH inhalation for 14 days, and the BER-inhaled and BER-intubated rats were intubated (100mg/kg) for the following three weeks. A novel object recognition task (NORt) was carried out on days 36 and 37. Rats were sacrificed for histological preparations after the behavioral tests. Neurotrophic factors, including GDNF and BDNF, were evaluated by immunofluorescence staining in the hippocampus.This experiment indicated a dramatic improvement in cognitive deficits associated with chronic METH abuse (Activation of neurotrophic factors after BER administration resulted in improvement of METH-induced cognitive deficits. Therefore, BER may be considered a promising treatment for METH users who experience cognition deficits.

Objective This study aims to evaluate the healing process of autografted mandibular bone defects in rats treated with zoledronate (ZOL). Subjects and methods A total of 180 Wistar rats were divided into four groups: group L received intravenous infusion of two doses of 0.06 mg/kg ZOL, nine weeks apart; group H received 0.06 mg/kg ZOL, while groups C and NC received normal saline at three-week intervals for nine weeks. Three weeks following the last infusion, a unilateral mandibular bone defect (5 mm) was created. Except in the NC group, all defects were repaired with autologous iliac bone graft. Fifteen animals from each group were sacrificed on postoperative Day 20, Day 40, and Day 60. Graft healing was scored using a histological grading system (ranging from 1 to 6). Results Histological evaluations performed on postoperative Day 60 showed that the mandibular defects were mainly repaired with fibrous tissue in the NC and H groups (93.00% ± 7.51% and 82.67% ± 13.08%, respectively) and with bone in the C and L groups (75.33% ± 14.20% and 92.67% ± 8.84%, respectively). The percentage of fibrous tissue and bone as well as the healing score of the NC and H groups were significantly different (P = 0.001) from those of the C and L groups. However, these were not different between neither the NC and H groups nor the C and L groups. Conclusion Based on the results of the present study the hypothesis can be established that there also might be a dose-dependent effect of ZOL on the healing of bone grafts in humans. This hypothesis has to be verified or rejected in clinical trials.

Background and Purpose: As a therapeutic enzyme, urate oxidase is utilized in the reduction of uric acid in various conditions such as gout or tumor syndrome lysis. However, even bearing kinetical advantage over other counterparts, it suffers from structural instability most likely due to its subcellular and fungal origin. Objectives: In this research, by using rational design and introduction of de novo disulfide bridge in urate oxidase structure, we designed and created a thermostable urate oxidase for the first time. Materials and Methods: Utilizing site-directed mutagenesis and only with one point mutation we constructed two separate mutants: Ala6Cys and Ser282Cys which covalently linked subunits of enzyme each other. Single mutation to cysteine created three inter-chain disulfide bridges and one hydrogen bond in Ala6Cys and two disulfide bridges in Ser282Cys. Results: Both mutants showed 10 °C increase in optimum activity compared to wild-type enzyme while the Km values for both increased by 50% and their specific activity compromised. The thermal stability of Ser282Cys increased remarkably by comparing Ala6Cys and wild-type enzymes. Estimation of half life for wild-type enzyme demonstrated 38.5 min, while for Ala6Cys and Ser282Cys were 138 and 115 min, respectively. Interestingly, the optimal pH of both mutants was broaden from 7 to 10, which could make them candidates for industrial applications. Conclusion: It seemed that introducing disulfide bridges resulted in local and overall rigidity by bringing two adjacent sites of enzyme together and decreasing the conformational entropy of unfolding state is responsible for the enhancement of thermostability.

Chronic liver injury and inflammation lead to hepatic fibrosis, cirrhosis, and liver failure. Transplantation of liver is the curative therapy for end-stage liver ailment. The common problem with liver transplantation like any other organ transplantation is organ shortage. The potential role for stem cell therapy to treat liver diseases has become recently topical in medical research because of the self-renewal characteristics expressed stem cells’ differentiation potential. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are MSCs with multiple differentiations potential. Because of its great resources, without any damage procurement, and less immunogenicity compared with other adult MSCs, WJ-MSCs promise to be a good exogenous cell candidate for tissue engineering. We hypothesize that use of human WJ-MSCs (hWJ-MSCs) xenotransplantation to the rabbit fetus liver to produce human liver tissue in animals’ fetus.

Background: Methamphetamine (meth) is recognized as a highly addictive psychostimulant. Currently, there are no available treatments for meth abuse, and no animal model of meth self-administration has been proposed to represent human meth self-administration. Objectives: We aimed to develop a model to study meth self-administration through inhalation in rats. Methods: Rats were placed in an inhaler apparatus (designed specifically for this purpose) for 15 min per day over two weeks. There were two levers in the cage. Pressing the passive lever had no outcomes. Whereas, for each active lever pressing, an infusion pump delivered 50 μL of meth or distilled water within two seconds. Meth was evaporated on a hot plate adjacent to the rat cage. After loading the drug over the hot plate, the blower fan was run, and the vaporized drug was blown by the fan into the rat cage. Then, meth-induced conditioned place preference and locomotor activity were assessed following 14 days of meth inhalation. The serum concentration of meth was also determined by gas chromatography-mass spectrometry. Results: In this model, the self-administration of meth through inhalation significantly increased locomotor activity, conditioned place preference, and plasma level of meth. Conclusions: We can conclude that the self-administration of meth through inhalation is a novel and effective route of self-administration. Our new protocol presents a promising tool for examining drug-seeking/taking behaviors and neural consequences in a noninvasive approach to reduce the stress of surgery and injection in laboratory animals and increase the validity of animal experiments.

To evaluate the effects of short-term teriparatide administration on healing of autologous bone graft in mandibular critical-size defects.A 5-mm mandibular bone defect was created and iliac bone graft was harvested in 135 rats. Rats were randomly divided into 3 groups of negative control (NC), control (C), and study (S). In groups S and C, iliac graft was placed in defect and 2 μg/kg/day teriparatide or saline, respectively, was administered for 20 days. In group NC, iliac graft was not transferred to the defect and saline was injected for 20 days. Twenty, 40, and 60 days after surgery, 15 rats in each group were euthanized and the healing process was histologically evaluated and scored using a grading system (1-6).In group NC, defects did not heal or were predominantly filled with fibrous tissue. At day 20, bone defects in both C and S groups contained a large area of graft particles, numerous collagen fibers and some areas of new trabeculae. At the day 40, defects in group S showed a larger bone graft area, more new bone formation, smaller connective tissue area, and a higher healing score compared to group C (P 0.05). At day 60, most of the defect in group S was filled with graft particles and mature bone while in group C, new trabecular bone formation was still underway (P 0.05).Teriparatide therapy improves healing of bone defects reconstructed with autograft by reducing bone graft resorption and enhancing new bone formation and maturation.

The aim of this study was to evaluate the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw (MRONJ). To induce MRONJ, a total of 120 rats received intravenous zoledronate 0.06 mg/kg once a week for 6 weeks and their right mandibular first molar was extracted. Eighty of 94 rats with MRONJ were randomly selected and underwent unilateral mandibular osteotomy to replicate a fracture. After surgery, the rats were randomly assigned to T (teriparatide-treated) and C (control) groups. Group T (n = 40) received subcutaneous injection of 2 μg/kg/day teriparatide and group C (n = 40) received the same volume of normal saline until sacrifice. Four and 8 weeks after surgery, 20 rats in each group were sacrificed. Fracture healing was scored using a histological grading system (1 to 10). In group C, at 4 weeks and 8 weeks post-fracture, fibrous and cartilaginous tissues and scant bone formation at the fracture site and lacunae without osteocyte in adjacent mandibular bone were seen. In group T, substantial amounts of new trabecular bone rimmed by osteoblasts and some areas of remodeled mature bone were seen. After 8 weeks, extensive replacement of trabecular bone with mature bone occurred. Except between C4 and C8 groups, the healing score was significantly different between all subgroups. Teriparatide therapy successfully improved mandibular fracture healing in rats with MRONJ. However, this study was limited by the use of an animal model whose anatomy, physiology, and drug metabolism might be different from humans. The present study showed that teriparatide therapy may be used adjunctive to surgery in the treatment of mandibular fractures in MRONJ patients.

Introduction To evaluate fracture healing in mandible of rats under zoledronate therapy. Methods A total of 135 Wistar rats were randomly allocated into 3 groups. Group L received two intravenous infusion of 0.06 mg/kg zoledronate 6 weeks apart. Group H received the same dose of zoledronate as group L once a week for 6 weeks and group C were treated with normal saline. Seven days after the last infusion, rats underwent unilateral mandibular osteotomy to replicate a fracture. Fifteen rats from each group were sacrificed 2, 4, and 6 weeks after surgery. Fracture calluses were examined and scored using a histological grading system (1 to 10). Results After 2 weeks, substantial woven bone and some lamellar bone were seen in control and L groups. In group H, healing was delayed and consisted of fibrous and cartilaginous tissue and some woven bone. After 4 weeks, most of woven bone in control group was replaced with lamellar bone but in group L, comparatively less bone remodeling occurred. In group H, healing process was nearly the same as that at 2 weeks. After 6 weeks, complete bone remodeling was seen in control group. In group L, bone remodeling was under way and in group H, histological findings were nearly the same as those at 2 and 4 weeks. Except for L and control groups at 2 weeks, healing score was significantly different between all corresponding groups. Conclusion Zoledronate therapy delayed healing process of mandibular fracture in rats in a dose-dependent manner.